chr19-45348004-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_177417.3(KLC3):c.623G>A(p.Arg208Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000634 in 1,608,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R208W) has been classified as Uncertain significance.
Frequency
Consequence
NM_177417.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLC3 | NM_177417.3 | c.623G>A | p.Arg208Gln | missense_variant | 5/13 | ENST00000391946.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLC3 | ENST00000391946.7 | c.623G>A | p.Arg208Gln | missense_variant | 5/13 | 1 | NM_177417.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000101 AC: 24AN: 237776Hom.: 0 AF XY: 0.0000851 AC XY: 11AN XY: 129202
GnomAD4 exome AF: 0.0000632 AC: 92AN: 1456690Hom.: 0 Cov.: 33 AF XY: 0.0000677 AC XY: 49AN XY: 724190
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.623G>A (p.R208Q) alteration is located in exon 5 (coding exon 4) of the KLC3 gene. This alteration results from a G to A substitution at nucleotide position 623, causing the arginine (R) at amino acid position 208 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at